Mitochondrial complex V expression and activity in cystinotic fibroblasts.

Contains fulltext : 69400.pdf (publisher's version ) (Closed access)Alterations in ATP metabolism have been proposed to be involved in the pathogenesis of cystinosis, the most common form of inherited Fanconi syndrome. A recent study showed normal activity of respiratory chain complexes I-IV with decreased ATP levels in cystinotic fibroblasts. Here, we show normal complex V expression and activity in mitochondria of cystinotic fibroblasts. This indicates that alterations in mitochondrial oxidative phosphorylation enzymes are not responsible for ATP decrease in cystinotic fibroblasts

The mitochondrial 13513G > A mutation is most frequent in Leigh syndrome combined with reduced complex I activity, optic atrophy and/or Wolff-Parkinson-White.

Contains fulltext : 52434.pdf (publisher's version ) (Closed access)The m.13513G > A transition in the mitochondrial gene encoding the ND5 subunit of respiratory chain complex I, can cause mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) and has been reported to be a frequent cause of Leigh syndrome (LS). We determined the frequency of the mutation in a cohort of 123 patients with reduced complex I activity in muscle (n = 113) or fibroblast (n = 10) tissue. We describe a Pyrosequencing assay for rapid detection and quantification of the m.13513G > A mutation. Two patients with the mutation were identified; both had LS, optical atrophy and a Wolff-Parkinson-White Syndrome (WPWS)-like cardiac conduction defect. The clinical presentation of the m.13513G > A mutation is discussed. We conclude that the m.13513G > A mutation seems not as frequent as previously suggested and is most likely to be present in patients with Leigh (-like) syndrome combined with a complex I deficiency, optic atrophy and/ or WPWS. In addition, we confirmed that the adjacent m.13514A > G mutation is a rare cause of LS or MELAS since no cases with this transition were found

Mutation detection in four candidate genes (OXA1L, MRS2L, YME1L and MIPEP) for combined deficiencies in the oxidative phosphorylation system.

Contains fulltext : 47516.pdf (publisher's version ) (Closed access)Mitochondria are the main energy-producing organelles of the cell. Five complexes embedded in the mitochondrial inner membrane, together constituting the oxidative phosphorylation (OXPHOS) system, comprise the final steps in cellular energy production. Many patients with a mitochondrial defect suffer from a so-called combined deficiency, meaning that the enzymatic activities of two or more complexes of the OXPHOS system are decreased. Numerous mutations have been described in nuclear genes that are involved in the functioning of a single complex of the OXPHOS system. However, little attention has been paid to patients with a deficiency of more than one complex of this particular system. In this study we have investigated four nuclear genes (OXA1L, MRS2L, YME1L and MIPEP) that might be involved in the pathology of combined enzymatic deficiencies of the OXPHOS system. Based on the results of yeast knockouts of these four proteins, we have sequenced the open reading frame of OXA1L in eight patients with an enzymatic deficiency of complexes I and IV. MRS2L, YME1L and MIPEP have been sequenced in three patients with a combined defect of complexes III and IV. No mutations were detected in these patients, showing that at least in these patients the OXPHOS system deficiency cannot be explained by a mutation in these four genes